Genesis of Eden

The major ethical issues arising from recent advances in biological
science are:

Human embryo research

The misuse of genetic screening

The release of genetically engineered microbes, plants and
animals into the environment

The modification of genes in the human germ-line

We will consider each of these issues in tum.

Human embryo research has been the subject of extensive
debate for some years. In some countries it is prohibited, in
others it is not. The main problem is due to the lack of consensus
on a basic human question: when does a fertilized human egg become
a human being? This is a fundamental ethical question because
a human being has human rights, including the right-tolife. 'Me
Catholic Church and many other religious groups strongly oppose
abortion. For them life starts from the fertilized egg, so abortion
is murder, and for people with these beliefs, human embryo research
is absolutely unacceptable. The USA is a country which since 1973
has had liberal abortion laws. The Supreme Court, in the case
of Roe vs. Wade, ruled in 1973 that any woman has an unrestricted
right to abort a foetus during the first 3 months of pregnancy.
There are about 1.5 million legal abortions carried out in the
USA each year. This being so, why should not some of these millions
of aborted foetuses be used for research, instead of being incinerated?
Such is indeed allowed in the USA, but other countries do not
allow such research. This is, however, an ethical problem, to
which scientific knowledge has little relevance. Biologically,
there is nothing more special about a fertilized egg than an unfertilized
one. Life is a continuum.

Genetic screening is an issue that will continue to
be discussed for many years to come. Points of issue include whether
genetic screening of embryos should be permitted. This procedure
allows the detection of a defective gene in an embryo. In many
countries there is already a widespread programme to screen for
the chromosome abnormality that leads to Down's syndrome. Gene
technology will allow many more conditions to be screened. Ethical
problems are also raised by the genetic screening of new-bom babies.
In some states of the USA, including Pennsylvania, every child
bom is screened for a battery of diseases including Duchenne muscular
dystrophy, a disease which leads to death before the twenties
and for which there is no cure known. We think that this is a
very dangerous practice not only because it can distress parents
who have not asked to know the future of their children, but also
because these genetic data have the potential to be misused by
insurance companies and employers. This knowledge may stigmatize
and marginalize people who had the bad luck to have a defective
gene. In a human society, which so often mistrusts those who are
different, a genetic passport can be a huge handicap. Perhaps
President Lincoln would never have been elected, if' his political
adversaries could have publicized the fact that he had the 'bad'
gene which causes the Marfan syndrome, a condition caused by the
possession of a dominant autosomal gene which results in ocular,
skeletal and cardiovascular abnormalities. On the other hand,
some genetic tests like that for phenylketonuria (see Chapter
10) need to be carried out because there is an effective treatment
which prevents its deleterious etyects. We think, like several
eminent human geneticists, that mandatory genetic tests should
be allowed only in those cases where the genetic disease can be
cured. The third problem arises from the genetic screening of
adults. Such tests should never be mandatory, but only carried
out with the consent of the individual, and even then the results
should be kept secret. This is the only way to ensure that there
is no discrimination against the carrier of'defective genes.

The release of genetically engineered organisms into
the environment could cause unexpected environmental problems.
We need to realize that it is possible to make combinations of
genes in organisms in a way that would be impossible by natural
selection. How do we decide it' a transformed organism might upset
the balance of ecology in a particulaienvironment? Could for example,
a bacteria, genetically engineered to eat oil spilled in the sea,
in a few years become a fish pathogen? Might the pathogenicity
start slowly, like the eftect of DDT, and then build up to cause
a catastrophe? The second aspect of the release of genetically
engineered organisms that has to be appreciated is that they are
alive. In the case of chemicals which are found to have undesirable
effects, it is possible to stop their use. Living organisms can
reproduce themselves so stopping their use may not help. The only
transformed organisms which should not be a threat are ones which
require human help to survive. We do not know if all the thousands
of organisms which have already been transformed have this peculiarity.
The business of transforming genomes is exploding so rapidly that
we do not have an overview of the problem.

The last issue is the biggest of all. Should we try to change
or add genes in the human germ line, the cells in our bodies
that have the potential to make gametes? Changes to the germ line
therefore have the potential to be inherited. We should make it
clear that it is not yet possible, mainly for technical reasons,
to transform human germ cells genetically. But what is not possible
today can be possible next year or in 5 years. Predictions are
very difficult to make in science. Therefore it is necessary to
discuss this problem now. Many gene therapists believe that the
best gene therapy is not one which modifies somatic cells but
that, if it is technically possible, it would be better to modify
the germ line. Genetically speaking this may be correct, although
many of the defective genes which affect humans arise as a result
of new mutations and so 'cueing' humans of mutant genes will not
be as easy as might be thought. Many people fear that once a technique
for modifying the germ line to treat genetic disease has been
introduced, it will slowly start being used for other things.
It is not immoral to have children with brown eyes so why can
we not introduce the gene which makes eyes brown? Or inactivate
a gene or two so that a girl had fair hair. Why not introduce
a gene which makes a boy 10 centimetres (4 inches) taller? To
be resistant to alcohol would be a good thing, let us add that
gene too. And what about the genes of intelligence, of courage,
of sport achievement, resistance to asbestos, the gene of happiness?
Do we want to change humankind? Who can decide which genes a future
human being should have, the mother or the parents or the state
or a committee of experts? Our new-found genetic knowledge raises
questions for all of us that are so novel and fundamental that
it is extremely difficult to know how the problem should be solved.
Certainly, committees of experts are important to give advice
but they should not make political decisions. There is also the
problem that many prominent scientists are strongly involved in
the biotechnology industry, and so their opinions may be biased.
The medical profession is not a guardian of morals and even less
a political institution. There are examples where the medical
profession in some countries at some times has failed to uphold
high moral values. Too many German doctors were willing to be
involved in the Nazi eugenics programme. Less well known is the
fact that the American Psychiatric Association until 1974, classified
homosexuality as a mental disease. The initiation of a programme
that allows the genetic modification of the human germ line, even
for the purposes of gene therapy, needs widely based and open
discussion. The decision cannot be delegated to experts or to
the medical profession. It is a political problem, but should
it be left to politicians? Some issues are too big to be left
to people who are often more concemed with re-election than with
the future of society. Perhaps such important ethical issues should
be decided by direct democracy. Should we use a Swiss style general
referendum to decide on such an issue? The great advantage of
this form of direct democracy is that everybody can participate
in the public discussion for months before the referendum is held.
The other advantage is that no one can say that she/he has no
power in the matter. But would it ever be possible for the majority
of people to be sufficiently informed to be able to vote rationally?
There are after all many examples in history of the tyranny of
the majority. Perhaps it is time for a novel form of democracy,
in which decisions are taken only by those who can successfully
complete a questionnaire that will test their background knowledge!
We end with another quotation from the Bible:

The Lord God ... said, 'The man has become one of us, knowing
good and evil; what if he now reaches out and takes fruit from
the tree of life also, and eats it and lives for ever?' So the
Lord God banished him from the garden of Eden to till the ground
... and he stationed the cherubim and a sword whirling and flashing
to guard the way to the tree of life. (GENESIS, 3: 22-24)

We must all now decide whether, having eaten the fruit of the
tree of knowledge, we wish to return to the Garden of Eden to
take fruit from the tree of life, changing human genes in the
hope of living for ever.

"Life would enter a new phase" says biophysicist
Gregory Stock - "one in which we seize control of our own
evolution".

IT IS only a matter of time. One day - a day probably no more
distant than the fhst wedding anniversary of a couple who are
now teenage ethearts - a man and a woman will walk mto an in-vitro
fertilisation clinic and make scientific history. Their problem
won't be infertility - the reason couples choose IVF now. Rather,
they will be desperate for a very special child, a child who will
elude a family curse. To create their dream-child, doctors will
fertilise a few of the woman's eggs with her husband's sperm as
as IVF clinics do today. But they will inject an artificial human
chromosome, carrying made-to-order genes like pearls on a string
into the fertilized egg. One of the genes will carry instructions
ordering cells to commit suicide. Then the doctors the place the
embryo into the mother's uterus. Left without the artifical genes
if her baby is a boy, when he became an old man he, like his father
and grandfather before him, would develop prostate cancer. But
the suicide gene will make his prostate cells self-destruct. The
man, unlike his ancestors will not die of the cancer. And since
the gene that the doctors give him will copy itself into every
cell of his body, including his sperm, his sonstoo will beat prostate
cancer. Genetic engineers are preparing to what has long been
an ethical Rubicon. Since 1990, gene therapy has meant slipping
a healthy gene into the cells of one organ of a patient suffering
from a genetic disease Soon, it may mean something much more momentous:
altering a fertilized egg so that genes in all of a person's cells,
including eggs or sperm also carry a gene that scientists, not
parents, bequeathed them. When the pioneers of gene therapy first
requested Government approval ,for their experiments in 1987,
they vowed they would never alter patients eggs or sperm. That
was then. This is now. One of those pioneers, Dr W. French Anderson
of the University of Southern California,- recently put the National
Institutes of Health on notice. Within two or three years, he
said, he would ask approval to use gene therapy on a foetus which
has been diagnosed with a deadly inherited disease.

The therapy would cure the foetus, before it was born. But
the introduced genes, though targeted at only blood or immune-system
cells, might inadvertently slip into the child's egg, (or sperm)
cells, too. If that happens, the genetic change would effect the
children to the nth generation.- "Life would enter a new
phase," says biophysicist Gregory Stock of UCLA "one
in which we seize control of our own evolution." Judging
by the 70 pages of public comments the national instutes have
received since Anderson submitted his proposal in September, the
overwhelming majority of scientists and ethicists oppose gene
therapy that changes the germ line (eggs and sperm). But the opposition
could be boulevard wide and paper thin. "There is a great
divide in the bioethics over whether we' should open this Pandora's
box says science-policy scholar Sheldon Krimsky of Tufts University.

Many bioethicists are sympathetic about using germline therapy
to shield a child from a family disposition to cancer or atherosclerosis
or other illnesses with a strong genetic component.'

As James Watson president of the Cold Spring Harbor Laboratory
and and co-discoverer of the double-helical structure of DNA said
at a recent UCLA, conference . We might as well do what we finally
can to take the threat of Alzheimers or cancer away from a family."

But something else is suddenly making it OK to discuss the
once forbidden possibility Of germline engineering. Molecular
biologists now think they have clever ways to circumvent the ethical
concerns that engulf this sci-fi idea.

There may be ways for instance to design a baby's genes without
violating the principle of informed consent. This is the belief
that no one's genes, not even an embryos - should be altered without
his or her permission.

Presumably a few people would object to being spared a fatal
disease. But what about genes for personality traits, such as
risk-taking or being neurotic?

But the child of tomorrow might have the final word about is
genes says UCLA geneticistJohn Campbell. The designer gene for
say patience could be paired with an of-off switch, he says. The
child would have to take a drug to activate the patience gene.
Free to accept or reject the drug, he retains informed consent
over his endowment.

There may also be ways to make an end run around the worry
that it is wrong to monkey with human evolution. Researchers are
experimenting with tricks to make the introduced gene self-destruct
in cells that become eggs or sperm. That would confine the tinkering
to one generation. Then if it became clear that eliminating the
genes for say mental illness also erased genes for creativity
that loss would not also become part of the man's genetic blueprint.

In experiments with animals Mario Capecchi if the University
of Utah has designed a string of genes flanked by the molecular
version of scissors. The scissors are activated by an enxyme that
would be made only in cells that become eggs or sperm. Once activated
the genetic scissors snip out the introduced gene and presto it
is not passed along to future generations. What I worry about
says Capecchi is that if we start mucking around with eggs and
sperm at some point - since this is a human enterprise - we are
going to make a mistake. You want a way to undo that mistake.
And since what may seem terrific now may seem naive in 20 years
you want a way to make genetic change reversible.

There is no easy technological fix ofr another ethical worry
however. With germ-line engineering only society's haves will
control their genetic traits. It isn't hard to forsee a time like
that painted in last year's film Gattaca where only the wealthy
can afford to genetically engineer their children with such 'killer
applications' as intelligence, beauty, long-life and health. "If
you are going to disadvantage even further those who are already
disadvantaged" says bioethicist Ruth Macklin of Albert Einstein
College of Medicine "then that does raise serious concerns".

But perhaps is not enough to keep designer babies solely in
Holywood's imagination. For one thing genetic therapy as done
today (treating one organ per child or adult) has been a bitter
disappointment. "With the exception of a few anecdotal cases"
says USCs Anderson "there is no evidence of a gene therapy
protocol that helps". But germ-line therapy might be easier
to make effective. Doctors would not have to insinuate the new
gene into millions of lung cells in say a cystic fibrosis patient.
They could manipulate only a single cell - the fertilized egg
- and still have the gene reach every of the person who develops
from that egg.

How soon might we design our children? The necessary pieces
are quickly falling into place. The first artificial chromosome
was created last year.

By 2003 the human genome project will have decoded all 3 billion
letters that spell out our 70,000 or so genes Animal experiments
designed to show that the process will not create horrible mutants
are under way.

No law prohibits germ-line engineering.

Although the National Institutes of Health now refuse to even
consider funding for it, the rules are being updated And where
there is a way there will almost certainly be a will.

"None of us" says Anderson "want to pass on
to our children lethal genes if we can prevent it. - that's what
is going to drive this."

At the UCLA symposium on germ-line engineering, two thirds
of the audience supported it. Few would argue against using the
technique to eradicate a disease that has plagued a family for
generations. As Krimsky says "We know where to start"
The harder question is do we know where to stop?

Evolution Extinguished NS
3 Oct 98 25

IF YOU put your ear to the tracks, you can hear the train coming.
In conference halls around the world, geneticists and developmental
biologists have been gathering to discuss what once was unthinkable-genetically
engineering human embryos so that they, and their children, and
their children's children, are irrevocably changed. These experts
are talking with remarkable candour about using germ-line engineering
to cure fatal diseases or even to create designer babies that
will be stronger, smarter, or more resistant to infections. Doctors
are already experimenting with gene therapy, in which a relatively
small number of cells-in the lungs, say-are altered to correct
a disease. Germ-line engineering, however, would change every
cell in the body. People would no longer have to make do with
haphazard combinations of their parent's genes. Instead, genetic
engineers could eliminate defective genes, change existing ones
or even add a few extra. Humanity would, in effect, take control
of its own evolution. So awesome is this idea, that until a year
or so ago, the taboo on human germline engineering was absolute.
But opinions have started to shift. Once barely considered a topic
for polite conversation among even the most gung-ho of geiieticists,
germ-line engineering of humans is becoming so much grist to the
mill of scientists gossiping around the coffee pot. Not that the
pillars of the scientific establishment agree on this emerging
technology, not by a long way. In a straw poll, researchers variously
described the idea of human germ-line engineering as "irresistible",
"morally questionable" or just plain "dangerous".
What they did agree on is that germ-line engineered humans are
likely to beconic a reality. Tampering with a human embryo to
create that can be passed from one to the next is still more or
less verboten 23 countries have signed a Council of Europe convention
that bans it and officials at the US Food and Drug Administration
promise not to give the go ahead without much public deliberation.
Despite this however, most experts say they would be surprised
if designer babies are not toddling around within the next 20
years or so. Gregory Stock, a biophysicist-turned- expert on technology
and society at the University of California, Los Angeles, helped
to organise a symposium in Marchcalled "Engineering the Human
Germ- line". The task? Not to look way into the future, but
at what we'll be faced with in the next decade or two. "There
is no way to avoid this technology," explains Stock, who
thinks that calling the evolutionary shots will create a happier,
healthier society. "The knowledge is coming too fast, and
the possibilities are too exciting." Public enthusiasm could
soon match Stock's: poll after poll shows that a sizeable minority
of paretits-sometitmes as many as 20 per cent-say tilat they see
nothing wrong with genetically altering their children for health
reasons, to give them an edge over the child at the next desk-or
even to stop them being homosexual. So what is shifting the mind-set
about human germ-line engineering from "never" to "well,
maybe"? The inain driving force, most experts agree, is the
new technologies rolling inexorably along the tracks. We are discovering
not ony what our genes do, but how to make precise changes in
themi Aild although the human genome isn't yet collipletely sequenced,
already the ditabases contain details of thousands of genes, and
of thousands of variations within them, along with information
about how these variations affect physical and emotional traits.
Added incentive comes, paradoxically, from frustrations with gene
therapy. Gene therapy promised to cure genetic disorders such
as cystic fibrosis and sickle-cell anaemia, and even common illnesses
such as cancer. But although the glitches are slowly being fixed,
few people have so far benefited from the procedure. The problem
is getting new genes into enough cells, and keeping them there
for long enough to do any good. With germ-line engineering you
have to tweak only one cell-a fertilised human egg-which is "infinitely
easier", says Leroy Hood, a molecular biologist at the University
of Washington in Seattle. "We have terrific ways to do that."
Once a genetic engineer has changed the genome of an egg fertilised
in a lab dish, the egg divides over and over again, forming all
the tissues of the body. Every cell will have exactly the same
genetic make-up as the altered egg.

Now and forever

Genetically engineered mice and farm animals have been around
for years and are used for everything from basic research to attempts
to create "humanised" animal organs for transplant.
But what might be considered a bonus in agricultural biotechnology-the
fact that any changes are present in the animal's sperm and eggs
(the "germ cells") and so will be passed on to succeeding
generations-is for many the most worrying thing about genetic
engineering in humans. The critics point out that if medicine
has played a bit part in our recent evolution-antibiotics, for
example, allow people with less than robUSt immune systems to
survive long enough to pass this trait into the next generation-genetic
engineering has the potential to be a star performer. One reason
for cold feet is that large scale genetic engineering could actually
rob society of desirable traits. What if the "disease"
genes in combination with other genes, or in people who are merely
carri ers, also help produce such intangibles as artistic creativity
or a razor-sharp wit or the ability to wiggle ones ears? Wipe
out the gene, and you risk losing those traits too. And while
no one would wish manic depression on anyone, society might be
the poorer without the inventiveness that many psychologists believe
is part and par cel of the disorder. in his book Remaking Eden,
Lee Silver, a biologist at Princeton University, goes as far as
to suggest that a century or two of widespread engineering might
even create a new species of human, no longer willing or able
to mate with its "gene poor" relations ("Us and
them", New Scientist, 9 May, p 36). "The potential power
of genetic engineering is far greater than that of splitting the
atom, and it could be every bit as dangerous to society,"
says Liebe Cavalieri, a molecular biologist at the State University
of New York in Purchase. Cavalieri, who has worked in the field
for more than 30 years, thinks it unlikely that the ugly side
of genetic engineering will stop development of the technology
in its tracks. "It is virtually inevitable it will get used
and for the most banal reasons possible-to make some money, or
to satisfy the virtuoso scientists who created the technology."
If esoteric worries about what may or may not happen in a genetically
engineered society are unlikely to change people's views, safety
issues could-at least until they are solved. "There is a
real risk of unforeseen, unpredictable problems," says Nelson
Wivel, deputy director of the Institute for Human Gene Therapy
at the University of Pennsylvania, and former executive director
of the National Institutes of Health Recombinant DNA Advisory
Committee. In gene therapy, genes are ferried into cells by modified
viruses or other means. It's a risky business, because genes can
get inserted in the wrong spot in the genome, killing the cell
outright or, far worse, triggering cancer. But at least with gene
therapy there is natural damage control-few cells pick up the
genes even when the procedure goes well, cancer only affects one
individual, and, as the procedure has always been carried out
long after birth, there's no chance of upsetting key developmental
genes. With germ-line engineering, on the other hand, there's
more scope for unpredictable, even monstrous, alterations. Take
the so-called "Beitsville pig". This pig, a thom in
the side of high-tech agriculturists and an icon for animal rights
activists everywhere, was engineered by scientists at the US Department
of Agriculture to produce human growth hormone that would make
it grow faster and leaner. The engineers added a genetic switch
that should have turned on the growth hormone gene only when the
pig ate food laced with zinc. But the switch failed. The extra
growth hormone made the pig grow faster, but it also suffered
severe bone and joint problems and was bug-eyed to boot. Of course,
unlike human experiments, slaughtering "failures" is
always an option for animal genetic engineers. Before genetic
engineering of humans can become a reality, each candidate gene
and its switches would need to be extensively studied in animals
first, and any changes would have to be made with a surgical precision
that reduced the chances of a "Beltsville human" to
just about zero. As it happens, over the past few years, molecular
geneticists have been busily developing the tools to do just this
sort of "genetic surgery". For years, genetic engineers
have altered farm animals by injecting genes into fertilised eggs
and then placing them in an animal's womb. But the technique is
far too unreliable to use in humans. Out of every 10 000 eggs
injected, roughly three make it to adulthood with the gene functioning
as planned. What's more, it is possible only to add whole genes,
not to fine-tune existing ones. With mice, the process is more
refined. Mice embryos contain embryonic stem (ES) cells that will
grow and divide in a flask. That allows the engineers to make
use of "homologous recombination", the process by which
DNA strands bind to, and sometimes replace, DNA strands of similar
sequence. With homologous recombination it is possible to make
tiny, surgically precise changes within genes, with the technique
depending in part on being able to sort through a large number
of ES cells, only picking out the ones that have taken the genetic
change in the correct place. Those cells are then added back to
an embryo, where they can form any part of the animal. The result
is a "chimera", an animal whose body contains both normal
and altered cells. To create an animal with the altered gene in
every cell, a chimera with the change in its eggs is bred with
one that has the change in its sperm-one reason the technique
can't be used in humans. But the efficiency of gene surgery is
improving so that fewer cells are needed to start with. That has
made it possible for several labs to try gene surgery directly
on fertilised mouse eggs, says Dieter Gruenert, a molecular geneticist
at the University of California, San Francisco, who is developing
just such a technique. The process is still in its infancy, but
it could one day make it possible to genetically engineer human
eggs, eliminating the need for crossbreeding. A more immediate
solution will probably come from an alternative way of generating
lots of identical embryonic cells: the technology that produced
Dolly & Co. Cloning relies on a combination of two new techniques.
First, grow cells taken from an adult or an embryo in a flask
under conditions that encourage them to divide and increase their
numbers, and then trick them into reverting to a nonspecialised
state with the potential to form an entirely new individual. Second,
fuse one of these cells with an egg from which the nucleus has
been removed, and implant this cutand-paste embryo into a womb.
The wrinkles still need ironing out, but these techniques promise
engineers the luxury of an inexhaustible supply of cells to attempt
genetic surgery upon, only transferring to an egg those nuclei
they know have been properly changed. And unlike the mouse ES
cells, these cells will generate an animal with the genetic change
in every cell. Born last year, Polly, a sheep with a gene for
a human clotting factor, was created in just this manner.

Batteries of genes

With the exception, perhaps, of Richard Seed-the Chicago physicist
who in January said he would open a human cloning clinic-no one
is openly attempting to develop cloning for humans. But hundreds
of genetic engineers are working to perfect its use in other mammals,
including primates. "None of the technologies [that will
allow human engineering] is being developed only for that purpose,
but when you put them all together, that is what you will have,"
says Wivel. Even so, whether or not it is combined with cloning
technology, "gene surgery" lets would-be human engineers
go only so far. They could tweak a gene here or add one there,
but they couldn't do much about characteristics such as intelligence,
say, or disease resistance, or athleticism, which are under the
control of numerous genes working in concert. For this, you'll
need a budding technology that could soon make it possible to
add whole batteries of genes to human cells. When it comes to
cell division, most of the DNA in each chromosome is irrelevant.
But to be copied properly and sorted into the two daughter cells,
a chromosome must have two types of highly specialised DNA sequences-one
somewhere in the middle called a centromere, and bits on either
tip called telomeres. Last year, Huntington Willard, a molecular
biologist at the Case Western Reserve Medical School in Cleveland,
Ohio, and his colleagues reported that they had created artificial
chromosomes in cultured human cells that replicated every time
the cells divided. "We cultured them for six months, and
they looked like perfectly normal chromosomes," say Willard.

Because these human artificial chromosomes (HACS) promise the
ultimate in genetic engineering, they have done more to fire up
discussion about human germline engineering than just about any
other technology. Once perfected, HACs will make it possible for
genetic engineers to ship complex custom-made genetic programmes
into human embryo cells. Each gene could come with control switches
geared to trip only in particular tissues, or when the patient
takes a particular drug. Suppose, for instance, that men in your
family tend to get prostate cancer at a young age. Insert into
your fertilised egg an HAC containing a gene for a toxin that
kills any cell that makes it, and two switches for that gene one
that is turned on only by prostate cells and another by ecdysone,
an insect hormone that humans cannot make. Nine months later,
you're delivered of a bouncing baby boy. Fifty years later, he
gets prostate cancer. He takes ecdysone, which activates the prostate
poison, killing every prostate cell in his body Even cancer cells
that have spread to other parts of the body should be wiped out.
It's scenarios like this-dreamt up by John Campbell, a molecular
biologist at the University of California, Los Angeles, who helped
to organise the March symposium-that make the promise of human
germ-line engineering so tantalising. Hood is convinced that the
benefits of germ-line engineering are going to be substantial:
"We could probably engineer people to be totally resistant
to AIDS, or to certain kinds of cancers. We might engineer people
to live much longer. I would say all these are good qualities."
Willard agrees that the prostate cell scheme, or others like it,
might someday be made to work. At the moment, his team is trying
to create HACs that contain specific human genes so that they
can check that the genes function normally in cell cultures. "Everybody
wants to [use artificial chromosomes] in mice," he says,
"But we're years away from even contemplating putting HACs
into humans." Still, when that day comes, as most experts
predict it will, who and what will be the first candidates for
human genetic engineering? Geneticists are more willing to kick
around the possibilities than ever before. Gruenert speaks for
many when he says that the crucial issue is whether germline engineering
would save lives and prevent suffering. "For medical reasons,
I have no problems," says Gruenert. "But for making
superwomen or supermen? I have some problems with that."
The first candidates for human genetic engineering are likely
to be children who could inherit a disorder that kills young,
is incurable both now and for the foreseeable future, and is caused
by a relatively simple defect. Tay-Sachs disease, which causes
the brain to degenerate in the first few years of life, is just
such a disease. Fix the gene, goes the argument, and you stop
the disease both in that child and all his or her offspring. If
the safety issues are resolved, the idea of wiping out such diseases
could sway the opinions of the public and regulatory agencies,
paving the way for the first attempt at human germ-line engineering,
says Jeremy Rifkin of the Foundation on Economic Trends in Washington
DC, a longstanding opponent of biotechnology. "I've seen
this pattern before in biotechFirst there is some discussion in
journals, then a conference, then they go ahead and do it. I think
there are protocols being readied now, and we'll see them within
a year or two."

Strange bedfellows

Rifkin may have some unusual allies in his fight against human
engineering. Many researchers who are otherwise decidedly pro-biotechnology
are vocal in their concerns about engineering humans. Allen Roses,
who heads Glaxo Wellcome's worldwide genetics research effort,
is emphatic that any attempts at germ-line engineering would be
"morally questionable". The milder-mannered Francis
Collins, director of the National Human Genome Research Institute
near Washington DC, says simply: "It is very hard to come
up with compelling scenarios of why you'd want to." Collins,
Roses and others take issue even with the idea of using genetic
engineering to prevent genetic disorders. They point out that
parents known to be at risk of certain serious genetic abnormalities
are already offered genetic testing and the option of an abortion
if their fetuses have the disorders. Using this approach, the
number of Tay-Sachs births has been reduced by more than 95 per
cent among American Jews. For women willing to have IVF, an embryo
can even be tested before pregnancy starts. Of course, repairing
rare genetic defects is not the only factor likely to endear genetic
engineering to the public. Who could resist the chance to bequeath
their

children freedom from Alzheimer's, cancer, heart disease and
diabetes? Then there's the possibility of cosmetic changes and
enhancements that have nothing to do with saving lives and preventing
disease. Many behaviourat traits, from cheerfulness to sexual
orientation, have already been linked, if tenuously, to variations
in single genes. Many more such links will be reported in the
near future. "There will come a time when we will understand
enough to manipulate even complex genetic systems," says
Hood. "For example, we will be able to dramatically affect
intelligence. That, I think, will be pretty irresistible."
"Evolution is being superseded by technology, and the time
scale will be far more rapid," says Stock. "Humans are
becoming the objects of conscious design." And no matter
how wild the idea of designer children sounds now, technology
has a way of making believers out of sceptics. Silver argues that
parents will provide the market forces that will eventually make
germ-line engineering of humans routine. When IVF was first being
developed in the 1970s, he points out, doctors and lay people
alike thought the idea absurd and repellent. Even though success
rates are still low, IVF created such demand among couples with
fertility problems that it has become widely accepted and commonplace.
For now, however, the regulative barriers are firmly down, even
as the research hurtles forward with breathtaking speed. Which
is perhaps why talk about engineering humans is now coming into
the open. It no longer makes sense to shy away from discussing
what we're going to do when all the technical obstacles are overcome,
and genetic engineering offers us the profound power to sculpt
our children-and the future of our species.

For more on the symposium 'Engineering the Human Germline",
see http://www.ess.ucia.edu/buge.

Ethical Dilemmas NS 17 Oct
98 Inside Science

Susan Aldridge

ETHICS is the study of the moral value of human conduct and
of the rules and principles that govern it. Often known as moral
philosophy, it seeks to distinguish between the good, what is
bad, and ways of implementing these rules. The thomy question
of how to define "good" and "bad" lies at
the heart of ethical decision making. The Greek philosopher Plato
said that the most important - and one of the most difficult -
question to answer in real life is "What is the good?"
It is hard to define exactly what we mean by ethics, even experts
disagree. Put simply, it refers to standards of behaviour governed
by what is agreed to be acceptable or correct. Basic categories
of ethical concem fall into two classes: intrinsic and extrinsic.
Intrinsic concerns deal with things that are thought to be wrong
in themselves, such as nuclear weapons and human cloning. Extrinsic
concerns involve the application of developments, neutral in themselves,
but open to misuse or the cause of harm to others, This classification
includes a new drug or an over-powered car. Many ethical arguments
hinge upon the weighing of risks against benefits. Risk benefit
analysis is the basis of an ethical system called utilitarianism,
whose exponents included philosophers Jeremy Bentham (1748-1832)
and John Stuart Mill (1806 - 1873). In a nutshell, utilitarianism
argues that things are right or wrong in proportion to the amount
of pleasure or pain they produce for communities or individuals.
Another school of ethical thought is based upon natural law. Here,
ethical decisions are made on the basis of how unnatural a scientific
development is. Under Natural Law, genetic engineering is seen
as intrinsically wrong, as is IVF. But the idea that natural is
good and unnatural is bad has weaknesses. Natural disasters, such
as earthquakes and volcanoes, cause immense damage and suffering,
and many plants contain potent toxins. You can also argue that
all scientific developments are, to an extent, unnatural. Natural
law also encourages respect for the natural world. And it touches
on the concept of human dignity: people should not be used as
a means to an end, but ascribed value in their ovm right. This
would forbid, say, the generation of embryos or fetuses to be
us ants surgery. it is not just biology and medicine that give
rise to ethical problems, of course. Take, for example, the 16ng
debate over nuclear power. Supporters say it is a clean source
of energy which can save the planet from global warming and provide
developing countries with the energy they need to get ahead. Critics
point out the risk of a major nuclear incident has been underplayed
by the industry.

ALL progress in science and technology has an impact on people's
lives. Often these effects are positive-antibiotics, computers
and electricity have made our lives safer, easier and more comfortable.
But inventions can bring suffering and injustice, such as nuclear
war, pollution and road accidents. How do we decide what is the
right and wrong use of science? These difficult choices lie in
the realm of ethics. Few of us would argue over the chemical formula
of sulphuric acid, or the right names for the bones in the human
skeleton, but when it comes to ethical questions there is often
disagreement on what is "right". Views on issues such
as genetic screening and clinical trials are affected by religion
and culture. And what is acceptable, changes over time. in 1967,
many condemned the first heart transplant as unnatural. But most
people now accept these operations as life savers. In 30 years
time, will we happily accept the transplantation of animal organs
to humans? Weighing benefits against risks can often provoke strong
feelings, as with the arguments over animal experimentation. Animals
are used in three main ways these days: in medicine, cosmetics
and transgenics. Each raises different questions about risk versus
benefits. Thousands of lives are saved every year through medicines
and surgical techniques that were first tested out on animals.
Research into cancer, mental illness and neurological disease
such as multiple sclerosis-all conditions for which there is a
clear need for new treatments-rely heavily on animal experiments.
In this case, most of us agree that the benefits in terms of reduced
human suffering outweigh the inevitable suffering inflicted on
the animals. In 1990, for example, 3.2 million animals experiments
took place. But a minority of animal experiments are carried out
to test cosmetics and toiletries. Here the balance seems to tilt
in the other direction. Some of these items are undoubtedly necessary,
but should animals suffer just to bring a new kind of makeup or
deodorant to supermarket shelves? Companies could instead be asked
to use ingredients already known to be safe. 'ftansgenic animals,
which carry genes from humans and other species, can be used to
test new treatments for diseases such as sickle-cell anaemia.
New drugs can be developed by creating transgenic sheep and cattle
that carry genes for human proteins that are produced in their
milk. Dolly, the cloned sheep, was created as part of this research
programme (although she is not herself transgenic). In this case,
the science is so new that judging long-term benefits and risks
is difficult. Some say that animals have rights and should never
be subjected to experiments, regardless of the benefits to humans.
They argue that even though chimpanzees, farm animals and laboratory
mice are not members of our species, this does not give us the
right to treat them as we please. Animal rights activists believe
humans are guilty of "speciesism", a notion suggested
in 1975 by the Australian philosopher Peter Singer. Even if we
argue that humans have greater rights, because they are rational
and self-conscious, we have to realise that chimpanzees show intelligence,
some selfawareness and possess a sophisticated social awareness.

Experiment or not The three "Rs"

ALERT to these ethical problems the British government brought
in the Animals Act in 1986 to control animal experimentation.
This incorporates the "Three Rs" principle developed
in 1959 by two researchers funded by the Universities Federation
for Animal Welfare. Rex Burch and William Russell had travelled
Britain interviewing scientists about good practice in the treatment
of experimental animals. The three Rs stand for reduction, refinement
and replacement. Reduction refers to cutting the number of animal
experiments, for example, by harmonising regulations between different
countries so that experiments do not have to be repeated in each
country. Refinement means extracting the maximum information from
the minimum number of experiments. And there are many possible
replacements for animal experiments, including the use of so-called
"lower" organisms-the horse shoe crab, for example,
tissue slices, cell cultures and computer models (see Figure 2).
In theory, a research scientist cannot use an animal in research
if the information could be obtained by one of these other methods.
In practice, few of the replacements are yet widely accepted as
valid alternatives to animal experiments. instead of animals,
we could use people in medical trials. Human clinical trials,
c@irried otit before l new drug or surgical treatment is niade
generally available, differ from animal tests in two ways. Firstly,
volunteers have to give their fully informed consent. Animals
cannot consent, for obvious reasons. And those recruited on clinical
trials do not usually include children or women of childbearing
age (because a fetus could be exposed to the drug) and prisoners.
Secondly, there should never be any intention to cause harm to
the volunteer. This is not true with animals where most are killed
at the end of the experiment, although there is a legal requirement
for pain to be kept to the minimum.

There is a serious ethical issue in human trials, however.
To get reliable information on a new treatment, it is necessary
to assign the volunteers either to a treatment group or a control
group that receives only a "dummy" treatment, or placebo
(see inside Science No. 65, "How a drug is born"). Patients
who are seriously ill, however, are understandably anxious to
receive the best treatment. Some doctors feel that depriving half
the patients of treatment is unacceptable; and it is sometimes
difficult to recruit patients to trials, even when the treatment
and control groups are swapped halfway through. Biotechnology
and genetic engineering (see Inside Science No. 105 "Growth
industry") raise many new ethical issues. Genes are, of course,
the basic material of these technologies, and commercially useful
genes can be found all over the world-in human populations, tropical
plants and even at the bottom of the ocean But who owns these
genes and who is going to benefit most from their exploitation?
The UN Convention on Biodiversity was agreed at the Rio "Earth
Summit" in 1992 seeks to address these concerns. It plans
to introduce and enforce ethical rules. Instead of biological
resources such as plants, cells and genes being regarded as the
common property of humanity, they now belong to their country
of origin. Before this, a drugs company from anywhere in the world
could bring plant and soil samples back from any other country
without any questions being asked. The company could screen its
samples for new antibiotics or painkillers, for example. If it
found anything worth exploiting, the rights in that discovery
belonged solely to the company. Now companies must enter into
formal agreements with governments before collecting any samples.
Some of the profits from a successful drug must now be ploughed
back into the country which gave rise to the original source material.
The ethical issue becomes even more sensitive when it comes to
dealing with human genes. The Human Genome Diversity Project is
sampling DNA from populations around the world. Part of the wider
Human Genome Project which was set up in 1990 to identify the
60 000 to 80 000 genes carried by humans, it will study differences
between the genetic make-up of ethnic populations, which, when
analysed alongside data for the prevalence of disease, may point
to genetic causes and possible treatments. However, Native American
groups in the US object to their genes being studied for fear
that the information will be used to exploit or discriminate against
them.

Improving nature: Plant genetics

PLANTS which have been genetically modified are already being
grown in open fields, and modified bacteria and viruses are often
used to carry genes into plants and animals. Developers want to
boost crop yields for the world's expanding population by protecting
the plants from pests, or to help the environment by enabling
a more efficient use of weedkillers. But critics point out that
making crops resistant to herbicides so that only weeds get killed
when herbicides are sprayed might encourage farmers to be careless.
If the herbicide does not harm their crop, they may stop worrying
about how much they use and perhaps be less careful about where
they apply it. There is another danger too: genetically modified
plants might breed with wild species and so spread their genes
far and wide. Supposing, for example, a gene for herbicide resistance
were to find its way into a weed. The creation of a superweed
that dominated the ecosystem would be an alarming development
and many people would like to wait until we know more about the
risks before proceeding further with plant genetic engineering.

Futuristic babies Beyond the test tube

AND it's not only plant reproduction that perturbs us. There
are now 13 ways to have a baby other than by sexual intercourse.
In vitro fertilisation (IVF) is a well-established technique,
producing so-called testtube babies. The technique now includes
the use of donor sperm and eggs, and embryo freezing. in future,
women may even be able to have babies by cloning their own body
cells. Assisted reproduction has the obvious benefit of bringing
the pleasure and joy of parenthood to childless women, whether
they are infertile single women, lesbians, postmenopausal women
or women wanting a dead partner's child. For some, these new candidates
for parenthood pose ethical problems. For example, one "cost"
of fVF is that children put up for adoption lose out if an infertile
couple opts instead for IVF, while the child of a postmenopausal
mother runs the risk of losing her care and support before reaching
adulthood. And all these techniques are expensive, so how can
we be sure that people with other medical conditions are not being
deprived of scarce resources as a result? Fertility drugs are
an essential part of IVF, but they make the rate of multiple pregnancy
increase from between I and 2 per cent to 25 per cent. it may
sound ideal to provide an infertile couple with a readymade family
in the form of twins, but there are many risks associated with
multiple pregnancy. The mother is more likely to suffer complications
such as high blood pressure, while the babies may be born prematurely,
possibly suffering lifelong health problems as a result. One way
around this problem is a technique called selective reduction:
where one or more of the fetuses is aborted to give the remaining
ones a better chance. For everyone involved, this is a difficult
decision to make.

The ethical dilemma here depends upon the status given to a
sacrificed fetus: whether or not it has equal rights with the
baby (or babies) that survives. These ethical issues resemble
those faced by other innovative medical procedures. But IVF and
related technologies have created new questions. Firstly, interference
with the processes of reproduction and birth is seen by many people
as being unnatural; some accuse the doctors of "playing God".
Then there are ethical issues about the parental rights and responsibilities
of all those involved in these new reproductive processes (see
Figure 3). When we separate biological and social parenting, it
has a radical impact on our ideas of what makes a family. IVF
may also lead to the creation of "spare" embryos, which
are not implanted into the uterus. How should we treat these?
Parents can opt to have these frozen for further use, donate them
to research or let them perish, but there was an outcry recently
when a woman proposed to store an embryo until it suited her to
carry it to term. It is also possible to create embryos in the
test tube specifically for research purposes. As with selective
reduction, attitudes towards embryo research depend upon the status
accorded to the embryo. In Britain, an embryo is seen in the eyes
of the law as rather less than a living child or adult, but still
worthy of respectful treat ment. Embryo research, which is permitted
up to 14 days after fertilisation, is strictly con trolled by
the Human Fertilisa tion and Embryology Authority. of course,
there has been a good deal of debate about the ethics of attempting
human cloning. We have to distinguish between cloning of cells
for possible medical uses on a patient and an entire cloned baby.
Cloned tissue could be used for transplants, in which case human
cloning would have some potential benefit-and would cut down on
animal experiments. But most people see the cloning of a new human
as unacceptable, mainly on the grounds that it is an offence against
human dignity and that each individual has a right to his or her
own genetic identity. in fact, there is already a market for clones,
but not human ones. People are already attempting to have their
pets cloned. But do animals have a right to their genetic identity?
Should cutting edge research like this be used to satisfy the
need for a pet? On the other hand, might cloned pets make people
liappy-as well as contributing to research?

Testing zone Hard choices

GENETIC advances have helped the treatment of inherited diseases.
Single gene disorders affect about I per cent of the population,
while many more common diseases, such as asthma, diabetes, and
cancer, have a genetic component. It is now possible to test high-risk
families, or populations, for the presence of many different defective
genes (Figure 5). As the Human Genome Project nears completion,
many more genes involved in disease will be discovered. Gene tests,
therefore, are certain to become more widespread in the future.
There is also the prospect of using gene therapy to insert healthy
genes into ordinary body cells (somatic cells), or even eggs and
sperm (germline cells). There are clear advantages to gene-based
medicine. Pre-natal diagnosis of a severe disorder like sickle-cell
anaemia allows the family the option of abortion. This saves the
whole family the burden of coping with an affected child. it also
saves the suffering of the child who would otherwise have been
born. Tests given to adults to assess their susceptibility to
cancer enables them to have more frequent medical checks. And
when tests on a member of an at-risk family prove negative, it
does enable them to make plans for the future with confidence.
Genetic testing also brings risks and costs. First, pre-natal
testing followed by termination deprives a child of the chance
of life, of some value, however great the suffering involved.
There is also the question of how serious a dis ease should be
before pre-natal testing is an ethical option. Would people not
want to have children with diabetes, say, if the relevant genes
were discov ered, even though people with diabetes can lead a
normal life with treatment? And maybe parents will soon have the
option of choosing embryos without genes which may be found to
influence baldness, low intelligence or even homosexuality? In
1997 a Gallup poll of British parents revealed that many would
opt for genetic enhancement of their children if they could. If
it were proved that genes for aggressive behaviour and homosexuality
existed: 18 per cent would choose an abortion against aggressive
behaviour and 10 per cent against homosexuality, while 5 per cent
would like a physically attractive child. Developments such as
these could lead to the development of a genetic underclass in
society, repeating the eugenic horrors of Nazi Germany. Fantastic
as these ideas may seem, we may see discrimination on genetic
grounds in the near future. Insurance companies could refuse policies
to people carrying faulty genes. There is also concern that employers
could use genetic tests to ensure a super-healthy work force,
thereby neglecting their responsibility to provide a decent working
environment. Genetic tests can also cause psychological suffering
in an at-risk family, particularly where incurable diseases, such
as familial Creuzfeldt-Jakob disease (CJD) or Huntington's disease,
are involved. Because these diseases develop in middle age, the
person testing positive may have no symptoms at the time, but
is suddenly facing a death sentence. They may already have had
children, who may be carrying the gene. There is also the issue
of whether to share the information with other family members.
This is why genetic testing is only done in specialist centres,
where full information and counselling are available. With so
many ethical issues raised by modern science, it is easy to understand
why there are now several university departments and legislators
who specialise in ethics. Their work will play an increasing role
in helping us to play our part in deciding between right and wrong
in scientific progress.

FURTHER READING Clones, Genes and Immortality; Ethics and the
Genetic Revolution by John Harris (Oxford University Press, 1998);
Attack of the Genetically Engineered Tomatoes: The Ethical Dilemma
of the '90s by Nicola Hamilton (Whittet Books, 1998); Improving
Nature? The Science and Ethics of Genetic Engineer' by Michael
J. Reiss and Roger 'ng

Straughan (Cambridge University Press, 1996). New Scientist's
special issue on genetic engineering will be published on 31 October
1998.

Susan Aldridge is the author of Magic Molecules (Cambridge
University Press, 1998).